The biochemical mechanisms of the phenotypic-specific restriction of chromatin function will be studied in a breast cancer model system of neoplastic progression. Particular reference will be paid to the preneoplastic lesion status in the model tissue system. Chromatin will be isolated from normal 15 day lactating mouse mammary glands, preneoplastic hyperplastic alveolar nodule (HAN) outgrowth line D1 and a mammary adenocarcinoma line 4331-D1 derived from HAN-D1. Functional chromatin fragments (euchromatin) will be isolated and characterized with respect to yields, composition, sterically available "free" DNA content and the ability of the fragments to prime for in vitro DNA-dependent RNA synthesis. The immunospecific nature of the DNA-Protein complex comprising the euchromatin fragments of normal, preneoplastic, and neoplastic mammary gland tissues will be tested by quantitative immunoassay. The extent of cross-reactive competency characteristic of the antisera produced against the DNA-Protein complexes will be evaluated. The heterogeneity of the antisera will be selectively depleted in non-specific antibody content by affinity immunoadsorbtion using heterologous tissue chromatin components. Chromatin components of the neoplastic progression series will be employed as immunoadsorbents to select for tumor- and/or HAN-specific antisera. The demonstration of either tumor-specific or HAN-specific antiserum related to certain DNA-Protein complexes in chromatin may permit the development of immunoassay methods for detecting the presence of preneoplastic or neoplastic lesions at early stages of progression. This finding would have wide practical application in pathology and chemotherapy. BIBLIOGRAPHIC REFERENCES: McClure, M.E. and Medina, D. (1975). "Similarity of Chromatin Non-Histone Protein Contents during Breast Neoplasia in the Mouse", Proc. Am. Ass. Cancer Research, 16, 204. McClure, M.E. and Medina, D. (1975). "Chromatin Non-Histone Protein Variations during Neoplastic Progression in Mouse Mammary Tissues", Proc. Am. Assoc. Cancer Research.